Division of Renal Disease, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Am J Physiol Renal Physiol. 2022 Jul 1;323(1):F48-F58. doi: 10.1152/ajprenal.00021.2022. Epub 2022 May 30.
Silica nanoparticles (SiNPs) released during the burning of sugarcane have been postulated to have a role in chronic kidney disease of unknown etiology. We tested the hypothesis that pristine SiNPs of the size present in sugarcane might cause chronic kidney injury when administered through the lung in rats. We administered 200- or 300-nm amorphous SiNPs twice weekly (4 mg/dose), or vehicle by oropharyngeal aspiration for 13 wk to rats followed by euthanasia after an additional 13 wk (26 wk total). Tissues were evaluated for the presence of SiNPs and evidence of histological injury. Both sizes of SiNPs caused kidney damage, with early tubular injury and inflammation (at ) that continued to inflammation and chronic fibrosis at despite discontinuation of the SiNP administration. Both sizes of SiNPs caused local inflammation in the lung and kidney and were detected in the serum and urine at , and the 200-nm particles were also localized to the kidney with no evidence of retention of the 300-nm particles. At , there was some clearance of the 200-nm silica from the kidneys, and urinary levels of SiNPs were reduced but still significant in both 200- and 300 nm-exposed rats. In conclusion, inhaled SiNPs cause chronic kidney injury that progresses despite stopping the SiNP administration. These findings support the hypothesis that human exposure to amorphous silica nanoparticles found in burned sugarcane fields could have a participatory role in chronic kidney disease of unknown etiology. Inhalation of silica nanoparticles (SiNPs) released during the burning of sugarcane has been postulated to have a role in chronic kidney disease of unknown etiology (CKDu). We administered 200- and 300-nm amorphous SiNPs to rats by aspiration and observed kidney damage with tubular injury and inflammation that persisted even after stopping the SiNP exposure. These findings support the hypothesis that human exposure to SiNPs found in sugarcane ash could have a participatory role CKDu.
燃烧甘蔗时释放的二氧化硅纳米颗粒（SiNPs）被认为在病因不明的慢性肾病中起作用。我们测试了一个假设，即在肺中给予与甘蔗中存在的大小相同的原始 SiNPs 时，可能会导致大鼠慢性肾损伤。我们通过口腔抽吸每周两次给予大鼠 200nm 或 300nm 非晶态 SiNPs（4mg/剂量），或载体，共 13 周，然后在额外 13 周后（共 26 周）安乐死。评估组织中 SiNPs 的存在情况以及组织学损伤的证据。两种大小的 SiNPs 均导致肾脏损伤，早期肾小管损伤和炎症（在）持续至炎症和慢性纤维化尽管 SiNP 给药停止。两种大小的 SiNPs 均导致肺部和肾脏的局部炎症，并在和时在血清和尿液中检测到，200nm 颗粒也在肾脏中定位，没有 300nm 颗粒的保留证据。在，肾脏中 200nm 硅的清除率有所提高，尿液中的 SiNPs 水平在 200nm 和 300nm 暴露的大鼠中均降低，但仍有显著意义。总之，吸入 SiNPs 会导致慢性肾损伤，尽管停止 SiNP 给药后仍会进展。这些发现支持这样的假设，即人类暴露于燃烧甘蔗田中发现的无定形二氧化硅纳米颗粒可能在病因不明的慢性肾病中起作用。吸入燃烧甘蔗时释放的二氧化硅纳米颗粒（SiNPs）被认为在病因不明的慢性肾病（CKDu）中起作用。我们通过吸入将 200nm 和 300nm 无定形 SiNPs 给予大鼠，并观察到肾小管损伤和炎症引起的肾脏损伤，即使在停止 SiNP 暴露后，这种损伤仍持续存在。这些发现支持这样的假设，即人类暴露于甘蔗灰中发现的 SiNPs 可能在 CKDu 中起作用。
